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Sequence Diversity andAntibody Response to Autologous and Heterologous MSP2 Antigens in a Prospective Malaria Immunology Cohort

Malaria, caused by the Plasmodium parasite and transmitted by mosquitoes, kills almost half a million people each year. Drug resistance in both the parasite and its vector make preventative measures increasingly important, and a fully protective vaccine is absolutely necessary to eradicate the disease. However, genetic diversity of the parasite makes vaccine development difficult. One of the best vaccine candidates is MSP2, a surface protein present during the blood stage of P. falciparum infection. Antibodies, which are important for natural immunity, have been shown to bind MSP2 and prevent parasite infection of blood cells. The purpose of this study was to analyze MSP2 sequence diversity in a cohort of patients infected while traveling or living in sub-Saharan Africa, and to investigate patient antibody responses to MSP2 variants infecting other individuals. Parasite isolates from our cohort were made up of 47% 3D7 alleles and 53% FC27 alleles. Protein sequences showed similar levels of conservation within allelic families, and blocks of conserved amino acids between different variants suggest there may be epitopes that can induce antibody production targeting multiple variants. Antibody reactivity tests suggest the variable region of MSP2 is important for antibody binding to variants of the same allelic type, while the conserved region is important for reactivity to different allelic types. This thesis gives evidence to the importance of including epitopes from conserved and variable regions of both MSP2 allelic families in order to induce strain-transcending immunity against P. falciparum malaria. / A genomic surveillance platform for indel-rich genes from Plasmodium spp. using long-read amplicon sequencing

Identiferoai:union.ndltd.org:UPSALLA1/oai:DiVA.org:uu-446805
Date January 2021
CreatorsZerebinski, Julia
PublisherUppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, Karolinska Institutet
Source SetsDiVA Archive at Upsalla University
LanguageEnglish
Detected LanguageEnglish
TypeStudent thesis, info:eu-repo/semantics/bachelorThesis, text
Formatapplication/pdf
Rightsinfo:eu-repo/semantics/openAccess

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